ATG5/7参与METH和HIV-1Tat蛋白协同诱导的树鼩中脑神经元自噬  

METH and HIV-1Tat protein co-induced autophagy via ATG5/7 pathway in primary midbrain neuronal cells

作　　者：李娟 晏和熙[1] 李红梅 吕丽琼 曾晓锋 代解杰 LI Juan;YAN Hexi;LI Hongmei;LYU liqiong;ZENG Xiaofeng;DAI Jiejie(School of Basic Medicine,Kunming Medical University,Kunming 650500,China.;Chinese Academy of Medical Sciences/Peking Union Medical College,Institute of Medical Biology,Yunnan Innovation Team of Standardization and Application Research in Tree Shrew,Kunming 650118;School of Forensic Medicine,Kunming Medical University,Kunming 650500)

机构地区：[1]昆明医科大学基础医学院,昆明650500 [2]中国医学科学院/北京协和医学院医学生物学研究所,实验树鼩标准化与应用研究云南省创新团队,昆明650118 [3]昆明医科大学法医学院,昆明650500

出　　处：《中国比较医学杂志》2020年第3期20-24,共5页Chinese Journal of Comparative Medicine

基　　金：国家科技支撑计划项目(2014BAI01B00);国家自然科学地区基金项目(81960340,81660310,81560303);NSFC-云南联合基金重点支持项目(U1702282);云南省科技人才和平台计划项目(2017HC019);云南省教育厅项目(2019J1186);昆明医科大学大学生创新项目(2019-80)。

摘　　要：目的探讨METH和HIV-1Tat蛋白协同诱导树鼩中脑神经元自噬的可能机制。方法本文以树鼩原代中脑神经元为模型,采用Western blot和Real-time PCR法测定METH和HIV-1Tat蛋白治疗细胞后,细胞中ATG5/7蛋白和基因的表达。结果 METH和HIV-1Tat蛋白能够诱导树鼩原代中脑神经元自噬,两者具有协同效应,且通过调节ATG5/7基因表达上调ATG5/7蛋白,进而调控自噬。结论 ATG5/7基因参与了METH和HIV-1Tat蛋白诱导的树鼩中脑神经元自噬,这一结论为研究艾滋病脑病和自噬之间的关系提供了新的理论依据。Objective Although the clinical implementation of antiretroviral therapy( c ART) has significantly prolonged the lifetime of AIDS patients,HIV-associated neurocognitive disorders( HANDs) remain a critical concern in a considerable number of HIV-positive individuals. HIV-1 Tat protein is a viral protein released from HIV-infected cells,which may be one of the underlying mechanisms behind HANDs. Methamphetamine( METH) can penetrate the blood-brain barrier,damaging nerve cells and increasing the risk of HANDs. The combination of HIV-1 Tat and METH can induce autophagy and apoptosis in nerve cells,but the regulatory mechanism behind this has remained unclear. Methods In this study,the primary midbrain neurons of tree shrews were used to determine the expression of ATG5/7 proteins and genes induced by HIV-1 Tat and METH via Western blot and real-time PCR. Results HIV-1 Tat protein and METH induced autophagy in tree shrews’ primary midbrain neurons and had a synergistic effect. ATG5/7 genes were involved in this autophagy. Conclusions ATG5/7 genes are involved in HIV-1 Tat protein and METH-induced autophagy of nerve cells,which provides a new theoretical basis for studying the relationship between HANDs and autophagy.

关 键 词：HIV-1Tat蛋白 甲基苯丙胺 自噬 原代培养 树鼩 

分 类 号：R-33[医药卫生]